=formed by two residues from helices 2 (H2) and 5 (H5) and two residues form loop E (LE1 and LE2), found on either side of the NPA motif=The narrow pore acts to weaken the hydrogen bonds between the water molecules allowing the water to interact with the positively charged arginine, which also acts as a proton filter for the pore.
5th Year BS-MS
What is Aquaporin ??
• Aquaporin is a 28 kDa protein embedded in the
cell membrane in order to regulate the flow of
• presence of these water channels increases the
permeability to water of the cell membrane
• Thousands of millions of water molecules per
second pass through one single channel
• Found in all kingdoms of life including bacteria,
plants, and mammals
• 13 in mammals, 6 in kidney
• In plants- 4 families
• In the mid 1950s-water can pass through
• Till early 80s-there are some sort of selective
filter that prevents ions from passing through
the membrane while water molecules can
• In the mid-1980s Peter Agre studied various
membrane proteins from the red blood cells
and also found one of these in the kidney.
• Having determined both its peptide sequence
and the corresponding DNA sequence, he
realised that this must be the protein that so
many had sought before him: the cellular
• In 1992 Peter Agre at John Hopkins
University reported his unintentional
discovery of aquaporin, he earned a
Nobel Prize for his discovery in 2003 .
Crystallographic structure of the aquaporin 1 (AQP1) channel (PDB 1J4N)
• Aquaporin appear to assemble in membranes
as homotetramers in which each monomer,
consisting of six membrane-spanning α-helical
domains with cytoplasmically oriented amino
and carboxy termini.
• two well-known channel constriction sites in the
peptide are NPA motif and a second and usually
narrower constriction known as 'selectivity filter'
or ar/R selectivity filter.
Importance of Aquaporins
• Aquaporin are known to play a big role in
various aspects of normal body function.
• Many mammalian AQPs, including AQP1,
AQP2, AQP4, AQP5 and AQP8, function
primarily as bidirectional water-selective
• It is seen that most, if not all, significant
biological functions of the mammalian AQPs,
can be attributed to AQP facilitated water
and/or glycerol transport.
• In oocytes it transport glycerol and to some
extent urea, along with water.
• Several diseases such as congenital
cataracts and nephrogenic diabetes
insipidus are relate to mutations in
aquaporins, also fluid transport, brain
swelling, strokes, meningities, multiple
• A small number of people are found with a
deficiency of aquaporins and they
generally seem healthy, but they have a
defect in the ability to concentrate solutes
• Aquaporin water channels: molecular
mechanisms for human diseases1-by
Peter Agre, David Kozono
• Aquaporins at a glance byAlan S.